3.3. CFD analysis
Differences were observed between the culture results of the rotary bioreactor and reciprocal bioreactor. The differences seemed to be influenced by the physical properties of each bioreactor. CFD simulations were used to clarify the relationship between culture results and physical action. In general, low shear stress is required for animal cell culture; however, our study showed uniform floating and dispersal of cells, and appropriate stimulus to cells to also be important.
Fig. 4A shows the vector of rotary bioreactor with EE, and Fig. 4B–D show the vector at the impeller positions “top dead point”, “passing through middle point”, and “bottom dead point”, respectively, of a reciprocal bioreactor. In the rotary bioreactor, weak flow zone exists near the center, under the impeller; however, in the reciprocal bioreactor, flow pattern spreads throughout the entire culture vessel. Such flow, as in the reciprocal bioreactor, is very important for cell culture. Fig. 4E shows the shear stress in rotary bioreactor, and Fig. 4F–H show the shear stress at the impeller positions, as shown above. Although the most abundant shear stress (around 1 Pa, Fig. 5) was similar to each other, characteristic distribution curve possessing two peaks was drawn in reciprocal bioreactor. Most importantly, the stress generated by reciprocal motion was not continuous while that in rotary bioreactor was generated continuously. Industrial production using animal cell culture starts by switching to protein production when cell growth reaches a stationary state. Therefore, the damage that cells undergo while facing prolonged and continuous shear stress in rotary bioreactor is considered to be more serious than that caused by discontinuous shear stress in reciprocal bioreactor. Moreover, it is also undesirable for the cell environment, since shear stress creates in a non-uniform condition in the bioreactor.
As shown in Table 1, both maximum and average shear stresses in rotary bioreactor were found to be higher than that in the reciprocal bioreactor. In addition, the simulation showed a large variation in the shear stress and shear rate in the rotary bioreactor. Cells in rotary bioreactor are continuously exposed to such a stressful turbulence, and accumulate the damage to eventually affect their physiological condition. Thus, the physical characteristics of the reactor are reflected in the culture results.